Molecular epidemiology and phylodynamic analysis of enterovirus 71 in Beijing, China, 2009-2019

Abstract

Abstract Background: Enterovirus 71(EV71)-associated hand foot and mouth disease (HFMD) decreased dramatically in Beijing, during 2009-2019. This study was to investigate the epidemiological characteristics, evolutionary dynamics, geographic diffusion pathway and other features of EV71 in Beijing, China. Methods: We carried out a retrospective study of EV71-associated HFMD and its causative agent in Beijing, China during 2009-2019. Phylogenetic and phylogeographic methods based on the EV71 genome were used to determine the evolution features, origin, spatiotemporal dynamics. Positive selection sites in the VP1 gene were identified and exhibited in the tertiary structure. Bayesian birth-death skyline model was used to estimate effective reproductive number (Re). Results: EV71-associated HFMD decreased greatly in Beijing. From 2009 to 2019, EV71 strains prevalent in Beijing shared high homology in each gene segment and evolved with a rate of 4.99*10-3 substitutions per site per year. Genetic diversity of EV71 first increased and peaked in 2012 and then decreased with fluctuations. The time to the most recent common ancestor (TMRCA) of EV71 in Beijing was estimated around 2003, when the EV71 strains were transmitted to Beijing from the east China. Beijing played a crucial role in seeding EV71 to central China as well. Two residues (E145Q/G, A293S) under positive selection were detected from both VP1 dataset and P1 dataset. They were embedded within the loop of the VP1 capsid and were exposed externally. Mean Re estimate of EV71 in Beijing was about 1.007. Conclusion: With a decreased genetic diversity, EV71 was no longer the primary causative agent of HFMD in Beijing in recent years. Beijing and the east China played a crucial role in seeding EV71 to other regions in China. Low Re estimate of EV71 in Beijing implied that strategies of prevention and control of HFMD were performed effectively.